The objective is to study the role of antibodies to melanocytes in the pathogenesis of vitiligo. We have recently demonstrated that the majority of patients with vitiligo have antibodies to surface antigens on normal human melanocytes. These can be demonstrated by specific immunoprecipitation of radiolabeled melanocyte macromolecules and by indirect immunofluorescence on viable melanocytes. Using these techniques, we now wish to explore the extent and role of melanocyte antibodies in the pathogenesis of vitiligo. We shall initially examine the specificity of melanocyte antibodies, their occurrence in depigmentary diseases of the skin unrelated to vitiligo, and whether alterations in cellular immunity to melanocytes is present in vitiligo. Subsequently, we shall attempt to identify, purify and characterize the antigen(s) defined by melanocyte antibodies using SDS-PAGE analysis of specific immunoprecipitates and immunoabsorption techniques. The role of melanocyte antibodies in the pathogenesis of vitiligo will be evaluated by correlating their level to the extent, activity and course of vitiligo; by examining whether they can damage pigmented cells in vitro; whether they are deposited in lesions of vitiligo in vivo; whether they are present in relatives of patients with vitiligo or in animals with this disease; and by attempting to induce vitiligo in animals by passive or active immunization to melanocytes. Lastly, because the destruction of melanocytes in vitiligo is the goal of treating melanoma, we shall examine whether there is any correlation between melanocyte antibodies and the course of melanoma in man and whether melanocyte antibodies can influence the course of melanoma in animals. Hopefully, the results of these studies will define the extent of specific alterations in immunity which occur in vitiligo and whether these cause, or result from, the disease.